Our plastic fabrication infrastructure is located at three sites as noted above and possesses tools for rapid prototyping, microfabrication, nanofabrication, and metrology.
We have two machines to do rapid prototyping of microfluidic devices in plastics. These include a high precision micromill (KU, LSU, and UNC) and a laser milling system using both an excimer laser (UNC) and a CO2 laser (KU). The milling machine can spin carbide bits as small as 25 µm by spinning at extremely high revolution rates. The mill can be used to write structures directly into plastics or into soft metals such as brass, which can be subsequently used a molding tools for hot embossing or injection molding. Channel widths as small as 25 µm can be fabricated with aspect ratios of 4:1 and side wall roughness ~300 nm.
Laser machining, in particular laser ablation, can directly write structures into plastics with the smallest feature size of 5 µm and an aspect ratio of 5:1. The laser sources are either a KrF laser (248 nm) or an ArF laser (193 nm). The selection of laser type is predicated on the type of material serving as the substrate. For example, polycarbonate can be used with the KrF laser, which cyclic olefin copolymers or PMMA can use the ArF laser.
We have developed world-class fabrication (replication)
capabilities of plastic devices using a variety of techniques such as hot
embossing, imprinting, nanoimprint lithography (NIL), and injection molding
(also injection compression molding). In addition, we have great working
relationships with several commercial foundries such as Stratec.
Here are the replication tools we possess within the Center:
We have within the Center, several tools for metrology across many different length scales. For example, we have several AFMs for determining replication fidelity in nanofluidic devices including a new Shimadzu scanning probe microscope and a Keyence rapid scanning confocal microscope for performing non-contact profilometry. The Keyence uses a violet laser that allows for depth profiling around 100 nm.
We have developed assembly techniques, which consist of bonding a cover plate to a patterned microfluidic or nanofluidic substrate, using thermal fusion bonding. In the case of microfluidic devices, we take a cover plate made of the same material as the substrate, and heat both pieces to near their glass transition temperature (Tg), which can be done in a convection oven with the two pieces clamped together or in a precision press with heated platens, and apply a certain amount of pressure to the plastics. This results in minimal deformation of the underlying structures as noted in the picture above, which shows microchannels that are 25 µm wide and 150 µm deep. The process yield rate of using this technique is >95%.
In the case of nanofluidic devices, we use a hybrid-based approach, which consists of thermal fusion bonding a high Tg substrate to a low Tg cover plate. When using bonding temperature close to the Tg of the cover plate, we can generate process yield rates >90% even for devices containing nanostructures as small as 10 nm.
Following device assembly, we can activate the surface of the plastic to both make it more hydrophilic (i.e., wettable) and create functional scaffolds (surface-confined carboxylic acids) for the covalent attachment of biologics, such as recognition elements or enzymes, using standard EDC/NHS coupling chemistry. This can be accomplished by exposing the device to UV/O3 radiation using a very simple instrument.
We have placed in the public domain a number of publications that highlight our ability to not only fabricate microfluidic and nanofluidic devices, but also use them in compelling biomedical applications. For example, we have used our plastic-based microfluidic devices for ultra-fast PCRs, electrophoresis, electrochromatography, solid-phase extractions, ligase detection reactions for the detection of point mutations, micro-optics, solid-phase bioreactors, and the isolation of liquid biopsy markers (see the Liquid Biopsy section in this website for more information on this topical area).
In terms of nanofluidics, which is a relatively new area for us, we have leveraged our ability to build functional devices with sub-100 nm structures for such applications of electrophoresis analysis of both small and large molecules, stretching DNA to detect chemotherapy-induced damage, and a new application we are developing which involves a single-molecule DNA/RNA sequencing platform (being co-developed by our commercial partner, Sunflower Genomics, Inc.).
We have also used many of the discoveries emanating from the Center to develop integrated and modular mixed-scale systems that can perform multi-step assays in a fully automated fashion. The integrated system idea we are pursuing is a modular one, in which task-specific modules are connected to a fluidic motherboard. The connections of the modules to the motherboard is achieved using superhydrophobic seals. The modules can be used as standalone units as well. We are adopting a universal fluidic motherboard approach so that modules can be easily interchanged to change the function of the system.